Treatment Of Pituitary Adenomas Research Articles

Experience using temozolomide in the treatment of aggressive pituitary adenomas

Background. The term “aggressive pituitary adenoma” arose as a result of transforming the term “atypical pituitary adenoma”, which was used in WHO classification for pituitary adenomas with specifications of higher labeling index Ki-67 (≥3 %) and increased number of mitoses with expression of the p53 proteins. However, not all tumors with these features were aggressive, and currently, according to the European Society of Endocrinology Clinical Practice Guideline for the management of aggressive pituitary tumors and carcinomas (2018), aggressive pituitary tumors are labeled as tumors that have invasive and unusually rapid or clinically significant growth which occurs despite the use of standard treatment protocols (pharmacological, surgical and radiation). Till date, there are numerous papers in literature describing various schemes and indications for the use of temozolomide. The efficiency of ongoing therapy, according to different authors, varies from 29 to 81 %, with an average effectiveness ranging between 40–45 %. Aim. To present our own experience of using temozolomide in the treatment of patients with aggressive pituitary tumors. Materials and methods. Three patients were included in the study, one male (45 years old) and 2 females (61 and 29 years old). All three patients included in the study first underwent surgical resection followed by radiation therapy if no response / hormonal activity didn’t resume. The decision to start temozolomide protocol was held by concerned medical commission under supervision of local ethical committee. Results. All patients responded well to temozolomide therapy with decrease in the size of tumor and decrease in levels of prolactin in cases of prolactinoma. Conclusion. The most important step in treating patients with aggressive pituitary adenomas is their early diagnosis, which could be possible only if the specific identifying markers of aggressiveness were found, which unfortunately are not found yet.

Endoscope-assisted transcranial surgery for complex pituitary adenoma: a retrospective case series study with propensity score matching.

Surgical treatment of complex pituitary adenomas (PAs) presents a significant challenge. Here in, we compared the surgical outcomes between patients undergoing endoscope-assisted transcranial surgery and microscopic regimens to assess the safety and efficacy of endoscope-assisted transcranial surgery in treating complex PA. This retrospective case-control study was conducted at the First Affiliated Hospital of Soochow University, China. Clinical data were retrospectively analysed between January 2018 and January 2023. The primary outcome was gross total resection (GTR), and the secondary outcomes included recurrence, residual tumour volume, and patient status. Propensity score matching was used to account for group differences. We enrolled 73 patients, of whom 29 underwent endoscope-assisted transcranial surgery, and 44 underwent transcranial microscopic surgery. Compared with the microscopic regimen group, the endoscope-assistedgroup had higher postoperative Karnofsky Performance Scale (KPS) scores (p = 0.031), higher GTR rates (GTR: 79.3% vs. 50%, p = 0.023), and smaller tumour residual volume (residual tumour volume: 0.15 vs. 0.94, p = 0.029). After propensity score matching, the endoscope-assistedregimen was associated with increased odds of GTR rate, compared with the microscopic regimen (odds ratio: 3.65, 95% confidence interval: 1.06-12.54, p = 0.040). KPS score improvement at discharge was more evident in the endoscope-assisted group than in non-combined group. The endoscope-assisted transcranial surgery regimen offered increased GTR rates, higher postoperative KPS score, and less residual tumour than the non-combined regimen did, highlighting endoscope-assistedtherapy as the more favourable treatment approach for patients with complex PA.

Endocrine Outcome and Quality of Life After Transsphenoidal Resection of Pituitary Adenoma-A Prospective Randomized Single-Blinded Study Comparing Endoscopic Versus Microscopic Resection.

Endoscopic pituitary surgery might yield better endocrine outcomes compared to microscopic resection. We conducted a prospective, randomized, single-blinded study to compare the endocrine outcome and quality of life (QoL) of patients with newly diagnosed pituitary adenoma who underwent either endoscopic or microscopic transsphenoidal surgery (NCT03515603). Due to slow recruitment, this study had to be stopped prematurely. Out of 170 transsphenoidal pituitary surgeries performed during the study period, 36 patients were enrolled in this study. The primary endpoint was based on the development of a new hypopituitarism. Secondary endpoints included the extent of resection, complications, and QoL. Endoscopic surgery was performed in 47.2% (n = 17). A new hypopituitarism was found in 8.3% (n = 3). All these cases underwent microscopic resection. Arginine vasopressin deficiency was found in 2.7% (n = 1) after microscopic resection. Gross total resection was achieved in 94.4% (n = 34). No surgical complications or new neurological deficits were observed. QoL improved significantly after the surgery, as measured by EQ-VAS (p = 0.003). According to EQ-5D3L, QoL improved or remained unchanged in almost all patients. No significant difference was found in QoL between the endoscopic and microscopic groups. The endoscopic technique appears to offer benefits in the treatment of pituitary adenomas, particularly in terms of achieving a favorable endocrine outcome.

Temozolomide treatment in refractory pituitary adenomas and pituitary carcinomas.

Temozolomide (TMZ), a non-classical alkylating agent, possesses lipophilic properties that allow it to cross the blood-brain barrier, making it active within the central nervous system. Furthermore, the adverse reactions of the TMZ are relatively mild, which is why it is currently recommended as a first-line chemotherapy drug for refractory pituitary adenomas (RPAs) and pituitary carcinomas (PCs). Systematic evaluations indicate a radiological response rate of 41% and a hormonal response rate of 53%, underscoring TMZ clinical efficacy, particularly when combined with radiotherapy. Functional tumors demonstrate a higher response rate compared to non-functional tumors. While the optimal duration of TMZ treatment remains undetermined, studies suggest that longer therapy durations may lead to better prognoses. Additionally, prior to TMZ administration, it is advisable to conduct immunohistochemical analysis of O6-methylguanine-DNA methyltransferase (MGMT), MSH2, MSH6, MLH1, PMS2, and N-methylpurine DNA glycosylase (MPG) to assess the potential impact of repair mechanisms such as direct repair (DR), mismatch repair pathway (MMR), and base excision repair (BER) on TMZ treatment. The efficacy of TMZ analogs, combined TMZ therapies, and TMZ with nanomaterials following TMZ treatment failure remains uncertain. The involvement of experienced multidisciplinary pituitary teams in all management decisions for RPAs/PCs patients is essential.

Genetic and Functional Changes in Mitochondria in the Pituitary Adenoma: The Pathogenesis and Its Therapy

Pituitary adenoma is a common neoplasm of the pituitary gland. Although most pituitary adenomas are benign, they can pose significant challenges in terms of their consequences and prognosis due to their tendency to invade surrounding tissues and their effects on hormone secretion. The management of pituitary adenomas typically involves surgery, medical therapy, and radiotherapy, each of which has its own limitations. Mitochondria play a crucial role in tumor development and progression by regulating various metabolic processes and signaling pathways within tumor cells and the tumor microenvironment. Multiple studies have indicated that mitochondrial dysfunction is implicated in human pituitary adenomas. Furthermore, several compounds with therapeutic effects on pituitary adenomas have been reported to target mitochondrial function. In this review, we summarize recent studies that highlight the involvement of mitochondrial homeostasis imbalance in the biology of pituitary adenomas. We conclude that mitochondria may represent a promising therapeutic target for the treatment of pituitary adenomas.

The rate of postoperative hematoma following risk-adapted cessation of oral anticoagulation in patients undergoing endoscopic endonasal surgery for pituitary adenomas.

This study describes the management of patients on oral anticoagulation (OAC) undergoing endoscopic endonasal transsphenoidal surgery (EETS) and analyzes the risk of postoperative hematoma and epistaxis following treatment of pituitary adenoma (PA). Patients with OAC prior to EETS for PA were analyzed in a single center retrospective case series of consecutive patients with PA, who were treated between December 2008 and July 2022. Patient data (age, sex, clinical, endocrinology, tumor histology) were entered into a SPSS® database. The rate of postoperative hemorrhage (intracranial and epistaxis) and other perioperative complications were assessed. Of 305 patients, 20 patients were on OAC prior to EETS for PA. Indications included non-valvular atrial fibrillation (AF) in 10 patients and previous venous thromboembolic event (VTE) in 8 patients, in 2 patients had overlapping indications. Twelve patients on direct oral anticoagulants (DOAC) paused medication 1-3 days (43.6 ± 23.6h) before surgery, while phenprocoumon was paused 234 ± 123.55h (min 6, max 22 days) before surgery. Baseline characteristics such as age, sex, tumor growth direction, tumor volume, and largest diameter showed no significant differences. No significant increase in postoperative hemorrhage was observed in patients with OAC compared to those without. One patient on apixaban paused 48h before surgery experienced postoperative epistaxis. Among patients without OAC, one experienced intracranial hemorrhage and seven experienced epistaxis. Patients with OAC prior to EETS for PA have no increased risk for postoperative hematoma when OAC is paused based on individual risk assessment and recent general recommendations.

Surgical effect of the medial wall resection of the cavernous sinus for functional pituitary adenomas.

The surgical treatment of pituitary adenomas (PAs) is aimed at achieving maximal tumor resection, relieving the compression, and correcting the disorders of pituitary hormones. Parasellar dural invasion is a primary factor in the failure of the surgery. By comparing the two operations of tumor excision combined with resection of the medial wall of the cavernous sinus (MW) and simple tumor excision, we further confirmed the clinical effectiveness and safety of the resection technique of the MW. 41 patients with functional pituitary adenoma (FPA) were divided into two groups according to the operation. The experimental group consisted of 20 patients who underwent tumor excision combined with resection of the MW via endonasal transsphenoidal approach and 21 patients who underwent simple pituitary tumor excision as the control group. Both groups were followed up for 12 months and matched for age, sex, BMI, tumor type, Knosp grade, maximum tumor diameter, hypertension, diabetes, and coronary disease. Perioperative-related indicators, biochemical remission rates, tumor recurrence rates, and complications were assessed. A total of 21 medial walls were removed in 20 patients, 15 (71%) specimens had pathologically confirmed tumor invasion. Biochemical remission rates and average operative duration in the experimental group were more than in the control group (P < 0.05). The remaining perioperative indicators, complications, and tumor recurrence rates had no statistically significant difference (P > 0.05). The technique of the MW removal via endonasal transsphenoidal approach for FPAs is safe and effective, with a high biochemical remission. The average operative duration for MW removal may be longer than that for simple tumor excision.

Evidence of Significant Intratumoral Transcriptomic Heterogeneity in Non-functioning Pituitary Adenomas Based on Location and Texture.

Introduction Surgical resection remains a standard treatment of non-functioning pituitary adenomas (NFPA). These tumors have significant intratumoral variability of growth rates and texture hardness. This preliminary study aims to identify variations in gene expression of different locations and textures within the same tumor to better explain tumor pathophysiology. Methods NFPA tissue samples were collected from four non-consecutive surgical adult patients undergoing endoscopic endonasal resection and were sent for next-generation transcriptomics. Significantly differentially expressed (SDE) genes were analyzed and categorized using ontology within different locations of the tumor, tumor hardness, and across patients. Results Around 164 SDE genes were identified: 264 across tumor hardness and 68 across location marginality (core vs. edge). A total of 132 gene ontology annotations were matched to all SDE genes. Most of these annotations involved a combination of cell metabolism, cell-cell interactions, and cell division. Conclusions There was significant evidence of variations and uniqueness in intratumor genetic heterogeneity within different locations, tumor textures, and across patients. The tumor edge expressed higher cell-cell interaction genes such as cadherin-binding proteins. Soft portions of the tumor experienced an upregulation of anaerobic metabolism and cell division genes. The uniqueness of gene expressions can be tested for biological function, prospectively, with the potential targets for gene therapy.

Ends of the spectrum best practices for early detection and multidisciplinary management of acromegaly.

Acromegaly is characterized by an insidious clinical presentation and delayed diagnosis. Longer delays are associated with more comorbidities which can persist after treatment of the growth hormone-secreting pituitary adenoma (GH-PA). Surgery is the primary therapy of GH-secreting PA, which can lead to durable remission. However, approximately 50% of patients require medical treatment postoperatively. Survival normalizes after achieving biochemical control. This mini-review will address ends of the spectrum challenges in acromegaly, including delayed diagnosis and management of the residual tumor and persistent comorbidities. We synthesize relevant literature and present a case of acromegaly that highlights the complexity of clinical decision-making in the diagnosis and treatment of persistent acromegaly. Despite improved biochemical assays, most patients with acromegaly are diagnosed on average five years after initial symptoms. A high index of suspicion does not rely exclusively on acral enlargement, but also a constellation of manifestations and comorbidities suggestive of acromegaly. Medical therapy is required in patients with persistent biochemical disease. Somatostatin receptor ligands are the cornerstone of medical treatment and can be used alone or in combination with dopamine agonists and growth hormone receptor antagonists. Improved options of medical treatment and careful consideration of comorbidities enables individualized patient management. Reoperation and radiation are considered for tumor progression despite medical therapy. In rare cases of resistant and aggressive tumors, neuro-oncology expertise is required. Increased awareness through education targeting the multifaceted clinical presentation of acromegaly shortens the time to diagnosis and treatment. Multidisciplinary management by specialists increases the likelihood of biochemical and tumor control.

Outcomes Associated With Stereotactic Radiosurgery After Multiple Resections of Nonfunctioning Pituitary Macroadenomas: An International, Multicenter Case Series.

Stereotactic radiosurgery (SRS) represents an effective treatment for nonfunctioning pituitary adenomas (NFPAs). However, no data have yet been published regarding results of SRS on NFPAs after multiple previous resections. Retrospective multicentric data of patients diagnosed with NFPA and who underwent multiple resections (≥2) before SRS were reviewed and analyzed. The treatment interval spanned the period of 1992 to 2022. Cox regression and Kaplan-Meier curves were used to assess predictive factors and the probability of tumor control and hypopituitarism. Among the 311 patients (median age: 50.2 [IQR: 18.0] years), 226 (72.7%) had undergone ≥2 previous resections. The median margin dose was 14 Gy (IQR: 4.0 Gy), and the median tumor volume 3.6 cm3 (IQR: 4.8). Overall, the probability of tumor control after SRS was 93.3% (CI 95%: 89.9-96.9) and 86.7% (CI 95%: 81.1-92.6) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with a decreased risk of tumor progression (hazard ratio = 0.33, CI 95% = 0.15-0.75, P = .008). At a last clinical follow-up of 4.1 (IQR 6.1) years, 10.1% (30/296) developed at least 1 new hormone deficiency after SRS. The cumulative probability of new hormone deficiency was 6.1% (95% CI: 3.0-9.1), 10.3% (95% CI: 5.8-14.6), and 18.9% (95% CI: 11.5-25.8) at 3, 5, and 10 years after SRS, respectively. The average latency between SRS and development of new hormone deficiencies was 3.3 years (IQR 4.1). A maximum point dose to the pituitary stalk >10 Gy was associated with a new deficiency (hazard ratio = 4.06, CI 95% = 1.57-10.5, P-value = .004). For patients with NFPA with multiple previous resections, SRS offers effective local tumor control and a low risk of delayed hypopituitarism for managing these challenging adenomas. SRS should be strongly considered in patients with NFPA with 2 previous resections compared with considering a third resection.

Radiofrequency echographic multi-spectrometry and prolactinoma: case report

In case of prolactin-secreting pituitary adenomas, the attention of patients and physicians is drawn to the clinical manifestations of pituitary adenoma, including associated metabolic disorders. The success of conservative methods of treating prolactinomas, the development and implementation of new approaches to the treatment of aggressive and resistant pituitary adenomas allow us to focus on non-obvious pathological conditions accompanying prolactin-secreting adenomas. These include secondary bone metabolism disorders with decreased bone mineral density (BMD), leading to osteoporosis and low-traumatic fractures. The key to effective prevention and treatment of osteoporosis is timely and accurate diagnostics, but not all methods for determining BMD developed to date can be characterized in this way. This paper highlights the use of new methods for diagnosing osteoporosis in the context of its high risk in hormonally active pituitary adenomas, in particular in prolactinomas, using a real clinical case as an example

Sinonasal Complications of Combined Transseptal–Transnasal and Bilateral Transnasal Approaches for Endoscopic Endonasal Transsphenoidal Pituitary Surgery

BackgroundThe endoscopic combined transseptal–transnasal technique for pituitary adenoma excision is notable for enhanced postoperative functional outcomes. Our study compared the incidence of anterior nasal septal perforation and the resulting sinonasal complications between this method and the bilateral transnasal approach. MethodsUtilizing a retrospective cohort from a preeminent tertiary referral center, we analyzed 141 cases of endoscopic endonasal transsphenoidal surgery performed between March 2018 and May 2023. Outcomes for the transseptal–transnasal group (n = 71) and the conventional bilateral transnasal group (n = 70) were compared. Nasal endoscopy and computed tomography were used to assess anterior nasal septal perforation. Functional outcomes were assessed preoperatively and at 6 months postoperatively using the Connecticut Chemosensory Clinical Research Center (CCCRC) test, Cross-Cultural Smell Identification Test (CCSIT), Sino-Nasal Outcome Test-22 (SNOT-22), and nasal obstruction symptom evaluation (NOSE) ResultsThe transseptal–transnasal approach exhibited reduced rates of postoperative ear fullness (p < 0.001), along with fewer subjective complaints of smell/taste loss (p = 0.022) and thick nasal discharge (p = 0.008), compared to the conventional approach. However, objective smell test results were not significantly different between the two approaches (p = 0.243 and p = 0.454 for CCCRC and CCSIT, respectively). Additionally, although statistically insignificant, a higher incidence of anterior septal perforation was observed with the transseptal–transnasal approach (p = 0.067). ConclusionFor the surgical treatment of pituitary adenomas, the transseptal–transnasal approach offers several advantages over the bilateral transnasal method, particularly in reducing postoperative complications. However, this technique requires careful attention for preventing the occurrence of anterior septal perforation.

6823 A Puzzling Case: Complete Regression of Pituitary Macroadenoma

Abstract Disclosure: N.T. Mazengia: None. D.R. Vangipuram: None. S.K. Majumdar: None. Introduction: The natural course of nonfunctioning pituitary macroadenomas remains poorly understood, largely because the majority are surgically treated [1]. There are a few case reports describing the spontaneous regression of nonfunctioning pituitary macroadenomas. Here we describe a case of pituitary macroadenoma which completely regressed following childbirth and two months of cabergoline therapy. Case Presentation: A 25-year-old female presented with bilateral nipple discharge and persistently elevated prolactin levels ranging from 31µg/liter to 45.9 µg/liter (NV &amp;lt;25 µg/L). She did not have any signs and symptoms of hypo or hypersecretion of the pituitary hormones. All her pituitary hormone levels were within normal range. Initial MRI revealed a pituitary mass measuring 9x13x9mm (AP, TR, CC). Given her lack of symptoms, the decision was made to follow up without any intervention. A repeat MRI after one year showed the size of the mass to be 11x13x11mm. Two years after her initial diagnosis, the patient had a spontaneous pregnancy, during which she remained asymptomatic with normal pituitary hormone levels. She had Cesarean delivery at term with no complication. She was lost to follow-up for about two years after childbirth then presented with breast discomfort and galactorrhea at which time, she was started on cabergoline. A subsequent MRI done two months after the start of cabergoline showed asymmetric fullness of the pituitary gland on the right with no discrete measurable lesion. Conclusion: We currently lack a comprehensive explanation for the regression observed in our patient. Silent ischemia may have played a role, particularly considering the natural increase in pituitary gland size during pregnancy. We are not sure if the regression can be solely attributed to the two months of cabergoline treatment. In asymptomatic patients diagnosed with nonfunctioning pituitary macroadenoma, tumor regression can potentially occur through either a "wait and watch" strategy or medical management using dopamine agonists, specifically cabergoline. However, the use of cabergoline as a primary treatment for asymptomatic nonfunctioning pituitary adenoma warrants further investigation. This is especially crucial given that, in most cases, nonfunctioning pituitary macroadenomas tend to increase in size during follow-up without any intervention.

Long Term Effect of Gamma Knife Radiosurgery versus Surgical Excision on Pituitary Hormones in Patients with Non-Compressive Non-Functioning Pituitary Macro Adenomas: A Systematic Review

Abstract Background Pituitary adenomas (PAs) are the second most common brain tumors comprise around 10%– 25% of all intracranial tumors of all primary brain tumors. Their clinical classification is defined on the basis of hormonal level into; Non-Functioning adenomas (68.8%) and Functioning ones (31.2%). Aim of the Work Aim of the work is to compare the surgical approach vs gamma knife radiosurgery for treatment of non-functioning pituitary macro adenomas in all age groups. We highlight the feasibility of each treatment modality and evaluate its advantages and limitations regarding hormonal outcomes. Patients and Methods We searched PubMed, Google scholar search engine, Cochrane database of systematic reviews, EMBASE and science Direct, using the following keywords “Pituitary adenoma/tumor, endoscopy or endoscopic, non-functioning pituitary adenoma, skull base surgery, gamma knife, stereotactic radiosurgery, hormonal effect ”. The mentioned databases were searched for studies published during period from 1 January 2000 to 1 September 2023. Results The total number of patients in included studies was 1237 patients. The mean age of patients was 56.55 years (range 54.2 - 59 years). The mean follow up duration of the included studies was 10.94 months (range 6 - 12.7) months. The mean tumor size was 29.03 mm (range 24.8 - 36.3) mm. All the surgical studies patients were treated using endoscopic trans sphenoidal approach. Basic study details and patient characteristics treated with Gamma Knife Radiosurgery (GKR). Again, all the included studies were retrospective in nature. The total number of patients treated in the GKR studies were 243 patients. Across all studies, 51.85% of patients were men, and the median age was 59.75 years (range: 50–69) Conclusion Endoscopic trans sphenoidal surgery and gamma knife radiosurgery are valid options as a treatment of non-functioning pituitary macro adenoma, however endoscopic transsphenoidal surgery offer better hormonal outcomes and less adverse effects when compared to gamma knife radiosurgery.

Distinct clinical characteristics and prognosis of pediatric-onset growth hormone-secreting pituitary adenoma (GHPA) patients compared to adult-onset patients.

To explore the clinical characteristics, treatment, and prognosis of growth hormone-secreting pituitary adenoma (GHPA) patients with pediatric-onset, so as to facilitate clinical management. A retrospective cohort study was carried out between 102 pediatric-onset GHPA patients admitted to our hospital from January 2013 to June 2022 and 204 adult-onset GHPA patients who were randomly matched. GHPA with pediatric-onset was predominantly male, associated with higher proportion of genetic syndromes, longer course, and delayed diagnosis. Clinical symptoms of visual field defects and menstrual abnormality were more common. The pediatric-onset group exhibited higher growth hormone (GH) nadir during oral glucose tolerance test (OGTT), higher rates of hyperprolactinemia, larger maximum diameter of adenoma, and higher rates of optic chiasm compression, suprasellar invasion, and pituitary apoplexy. Hypertension, diabetes, and obstructive sleep apnea-hypopnea syndrome (OSAHS) were more common in the adult-onset group. Echocardiography results were similar between the two groups. The pediatric-onset group owned significantly higher treatment scores and proportions of multimodal therapy modality, more surgical complications, and a higher proportion of ki67 ≥ 3%. There was no significant difference in the final cure rate, but male patients with adult-onset had a worse prognosis. The recurrence rate was also similar between two groups. Hypopituitarism was more prevalent in the pediatric-onset group, while the adult-onset group had a higher incidence of other tumors. Pediatric-onset GHPA patients exhibit distinct clinical characteristics compared to adult-onset patients. Multimodal therapy modalities could help to achieve a cure rate comparable to that of adult-onset patients.

Approaches based on natural products and miRNAs in pituitary adenomas: unveiling therapeutic intervention.

Pituitary adenomas (PAs) are tumors originating in the pituitary gland, a small gland located at the base of the brain. They are the most common type of pituitary tumor, affecting approximately 1 in 10 people over their lifetime. Common symptoms include headaches, vision problems, hormonal imbalances, and weight changes. Treatment options depend on the type and size of the adenoma and may consist of medication, surgery, radiation therapy, or a combination. PAs are typically benign and slow-growing, but they can cause significant health issues if left untreated. Proper diagnosis and management by an experienced multidisciplinary team is important for achieving the best outcomes. Natural compounds like celastrol, curcumin, quercetin, apigenin, resveratrol, epigallocatechin gallate (EGCG), and genistein have shown the ability to inhibit cell growth, promote cell death, and suppress hormone activity in pituitary tumor cells, suggesting their potential as alternative or complementary treatments for PAs. MicroRNAs (miRNAs) are a kind of tiny RNA molecules that do not code for proteins and have a vital function in controlling gene expression. These 21-23 nucleotide-long molecules regulate gene expression by binding to complementary sequences in mRNA molecules, leading to mRNA degradation. miRNAs participate in a wide range of biological activities, including apoptosis, metastasis, differentiation, and proliferation. The research indicates that miRNAs play a crucial role in the pathogenesis, therapeutic approaches, diagnosis, and prognosis of PAs. This review article will provide a comprehensive analysis of the current understanding of the efficacy of naturally derived anti-cancer agents in the treatment of PAs. Furthermore, the study provides a comprehensive assessment of the miRNAs in PAs, their role in the development of PAs, and their potential application in the treatment of the condition.

Exosomal AFAP1-AS1 Promotes the Growth, Metastasis, and Glycolysis of Pituitary Adenoma by Inhibiting HuR Degradation

Exosomal long noncoding RNAs (lncRNAs), which are highly expressed in tumor-derived exosomes, regulate various cellular behaviors such as cell proliferation, metastasis, and glycolysis by facilitating intercellular communication. Here, we explored the role and regulatory mechanism of tumor-derived exosomal lncRNAs in pituitary adenomas (PA). We isolated exosomes from PA cells, and performed in vitro and in vivo assays to examine their effect on the proliferation, metastasis, and glycolysis of PA cells. In addition, we conducted RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, and ubiquitination assays to investigate the downstream mechanism of exosomal AFAP1-AS1. Exosomes from PA cells augmented the proliferation, mobility, and glycolysis of PA cells. Moreover, AFAP1-AS1 was significantly enriched in these exosomes and stimulated the growth, migration, invasion, and glycolysis of PA cells in vitro, as well as tumor metastasis in vivo. It also enhanced the binding affinity between Hu antigen R (HuR) and SMAD-specific E3 ubiquitin protein ligase 1 (SMURF1), resulting in HuR ubiquitination and degradation accompanied by enhanced expression of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). Moreover, HuR overexpression alleviated the exosomal AFAP1-AS1-mediated promotion of growth, metastasis, and glycolysis effects. These findings indicate that tumor-derived exosomal AFAP1-AS1 modulated SMURF1-mediated HuR ubiquitination and degradation to upregulate HK2 and PKM2 expression, thereby enhancing PA cell growth, metastasis, and glucose metabolism. This suggests targeting exosomal AFAP1-AS1 may be a potential strategy for the treatment of PA.

Surgical outcome of endoscopic endonasal approach as a modality of management for large and giant pituitary adenomas: a retrospective case series

BackgroundLarge and giant pituitary adenomas (defined as tumors of maximal diameter ≥ 3–3.9 cm and ≥ 4 cm, respectively) present considerable surgical challenges regarding the extent of resection and perioperative morbidity. Endoscopic endonasal resection is considered the most effective treatment for pituitary adenomas. It allows for better visualization, maneuverability, and access to distant and lateral tumor compartments, ultimately enhancing the extent of resection. This article evaluates our initial experience with endoscopic endonasal resection of large and giant pituitary adenomas. The clinical outcomes, perioperative complications, and extent of tumor resection would be specifically addressed.Patients and methodsThe primary goal of surgery was to decompress the optic pathways, and the secondary goals were to achieve maximal safe resection and hormonal control in hormone-secreting adenomas. The degree of tumor resection was classified as gross-total resection (100%), near-total resection (90–100%), subtotal resection (70–90%), and partial resection (< 70%).Results42 patients were included in this study. A good visual outcome achieved with 80% improvement in visual symptoms. Gross-total resection (GTR) was achieved in 19 patients (45.2%), near-total resection (NTR) was achieved in 12 patients (28.6%), subtotal resection (STR) in 6 patients (14.3%), and partial resection in the remaining 5 patients (11.9%). Subgroup analysis revealed that GTR, NTR rates were higher in large, compared to giant tumors. GTR, NTR rates of large adenomas were 59.3%, and 29.6%, compared to 20%, and 26.7% in giant adenomas respectively (p-value: 0.01428). Surgical complications were observed in 19 patients (45.2%) with CSF leakage being the most common complication (11 patients, 26.2%). Post-operative diabetes insipidus was observed in 5 patients (11.9%), major vascular injury in one case (2.4%), transient post-op 6th nerve palsy observed in 3 patients (7.1%), while two patients (4.8%) presented with post-operative paranasal sinuses infection.ConclusionsEndoscopic endonasal transsphenoidal resection of large and giant pituitary adenomas is a safe and efficient procedure. Large adenomas (3–3.9 cm) have excellent resection rates and lower complications than giant adenomas (≥ 4 cm), which may require extending our approach to achieve more tumor resection rates in the future. However, only adequate resection of these giant adenomas can be enough to achieve the main surgical goals of visual improvement, hormonal control, and decompression of surrounding structures.

Surgical treatment of cystic pituitary adenomas: literature-based definitions and postoperative outcomes.

To survey the applied definitions of 'cystic' among pituitary adenomas and evaluate whether postoperative outcomes differ relative to non-cystic counterparts. A literature search and meta-analysis was performed using PRISMA guidelines. Studies were eligible if novel data were reported regarding the applied definition of 'cystic' and postoperative outcomes among cases of surgically treated pituitary adenomas. Data were pooled with random effects meta-analysis models into cohorts based on the applied definition of 'cystic'. Categorical meta-regressions were used to investigate differences between cohorts. Among studies comparing cystic and non-cystic pituitary adenomas, meta-analysis models were applied to determine the Odds Ratio [95% Confidence Interval]. Statistical analyses were performed using Comprehensive Meta-Analysis (CMA, 4.0), with a priori significance defined as P < 0.05. Ten studies were eligible yielding 283 patients with cystic pituitary adenomas. The definitions of 'cystic' mainly varied between the visual appearance of cystic components on preoperative magnetic resonance imaging and a volumetric definition requiring 50% or greater of tumor volume exhibiting cystic components. Tumor diameter was seldom reported with an associated standard deviation/error, limiting meta-analyses. When the data were pooled in accordance with the definition applied, there were no significant differences in the rates of gross total resection (P = 0.830), endocrinologic remission (P = 0.563), and tumor recurrence (P = 0.320). Meta-analyses on studies comparing cystic versus non-cystic pituitary adenomas indicated no significant difference in the rates of gross total resection (P = 0.729), endocrinologic remission (P = 0.857), and tumor recurrence (P = 0.465). Despite some individual studies describing a significant influence of pituitary adenoma texture on postoperative outcomes, meta-analyses revealed no such differences between cystic and non-cystic pituitary adenomas. This discrepancy may be explained in part by the inconsistent definition of 'cystic' and between-group differences in tumor size. A notion of a field-standard definition of 'cystic' among pituitary adenomas should be established to facilitate inter-study comparisons.

Simultaneous resection of pituitary adenoma and clipping of aneurysm through endoscopic endonasal approach: a case report

Pituitary adenomas and intracranial aneurysms are prevalent neurosurgical conditions, but their simultaneous presence is uncommon, affecting only 0.5%-7.4% of those with pituitary adenomas. The strategy of treating aneurysms endovascularly before removing pituitary adenomas is widely adopted, yet reports on addressing both conditions at once through an endoscopic endonasal approach (EEA) are scarce. We present a case involving a pituitary adenoma coupled with an anterior communicating artery aneurysm. Utilizing the EEA, we excised the adenoma and clipped the aneurysm concurrently. The patient recovered well post-surgery, with follow-up assessments confirming the successful resolution of both the adenoma and aneurysm. We proved the feasibility of the EEA in the treatment of pituitary adenomas with anterior communicating artery aneurysms under specific anatomical relationships and close intraoperative monitoring.